Anesthetics delivery sites

In this section, we focus on how to determine DD sites by NMR. The specification of the DD sites in bilayers can be done by utilizing the NMR signals of both drugs and membrane lipids. An example of the delivery site determination is given for the case of two benzene derivatives, propylbenezene (PrBe) and benzyl alcohol (BzOH) in egg phosphatidylcholine (EPC) bilayers [46]. Alkylbenzenes are suspected to be endocrine disruptors, and BzOH is one of the local anesthetics. 

It has been generally accepted that anesthetics interact with membrane lipids as a primary step of anesthesia. The detailed mechanism of the anesthetic action is, however, still controversial. This is mainly due to the absence of specific information on delivery sites in membranes. The NMR data for the delivery site of drugs in membranes are of great use. 

Most recently, we have applied and H NMR to the delivery of local anesthetics from water to phospholipid bilayer membranes [48]. Preferential locations of the four drugs DBC-H+, PRC-H+, TTC-H+, and LDC-H+ in EPC SUV have been specified and compared. To specify the delivery sites of drugs on the atomic-site level from their... 

It is interesting that the different delivery sites of the drugs can provide a variety of anesthetic potencies. For example, the strongest and long-lasting anesthetic effect of DBC H+ can be combined with the specific trap in zone II. The penetration of DBC H+ into the hydrophobic bilayer interior, zone III, can be a cause of the toxicity. In contrast, I ROI 11, preferentially adsorbed on the hydrophilic surface of the bilayer, zone I, and easily desorbed in the aqueous phase, cannot induce the long-lasting anesthetic effect and toxicity. 

Injectable anesthetics act faster and are therefore best suited for induction of anesthesia and for short operative procedures. However recovery from injectable anesthetics is generally slower than with inhalation anesthetics. The high blood flow to the brain leads to rapid delivery of the anesthetics to their site... 

Since local anesthetics are capable of blocking all nerves, their actions are not limited to the desired loss of sensation from sites of noxious (painful) stimuli. Although motor paralysis can be desirable during surgery, it may also limit the ability of the patient to cooperate (ie, push) during obstetric delivery or ambulate without assistance after outpatient surgery. 

Inhalation Inhalation provides the rapid delivery of a drug across the large surface area of the mucous membranes of the respiratory tract and pulmonary epithelium, producing an effect almost as rapidly as by intravenous injection. This route of administration is used for drugs that are gases (for example, some anesthetics), or those that can be dispersed in an aerosol. The route is particularly effective and convenient for patients with respiratory complaints (for example, asthma or chronic obstructive pulmonary disease) as drug is delivered directly to the site of action and systemic side effects are minimized (see p. 219). 

Masters and Domb [250] reported on an injectable drug delivery system that uses liposomes [251] to release the local anesthetic, bupivacaine, from a liposomal matrix that is both biodegradable and biocompatible to produce SLAB. Bupivacaine due to its minimum vasodilating properties was preferred to other local anesthetics (e.g., lidocaine) allowing the released drug to remain at the site of injection longer [252]. Lipospheres are an aqueous microdispersion of water insoluble, spherical microparticles (0.2 to 100 pm in diameter), each consisting... 

The production and maintenance of the anesthetic state is believed by most to be dependent on the concentration, or partial pressure, of the anesthetic agent in yet unknown areas of the brain. Obviously, the concentration of the anesthetic agent in the gas mixture administered, as well as the rate and depth of respiration of the patient, will influence the rate of anesthesia induction. The rate at which delivery of anesthetic agents to these sites occurs is dependent on their physicochemical properties, particularly their solubility in lipid and blood. 

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